In recent decades, the prevalence of asthma in the US and other industrialized countries has increased dramatically. Chronic allergic lung disease (allergic asthma) accounts for a majority of asthma. Many studies have demonstrated that Th2 cells and Th2 cytokines including IL-4, IL-5, and IL-13 play an important role in the development of allergic lung disease and the downstream events, including inflammation, eosinophilia, mast cell accumulation/activation, and airway remodeling. However, less is known about the mechanisms that affect the development and maintenance of Th2 cells. The proliferation and differentiation of naive T cells is triggered by interactions with antigen presenting cells bearing cognate antigen. It is becoming increasing clear that the conditions surrounding this interaction influence T cell differentiation. This proposal will investigate the role that B cells have in shaping the T cell response during chronic allergic lung disease. In addition, the role of important innate molecules will be investigated for their contribution to the regulation of B cell antigen presentation. In these studies, we investigate the role of B cells in chronic allergic lung disease, with an emphasis on the role of B cells as antigen presenting cells. These specific aims will build a foundation for investigating the role of B cells in allergic disease, but these studies will have relevance for understanding the role of B cells in the immunology of other chronic diseases. RELEVANCE: Chronic allergic lung disease (asthma) is characterized by inappropriate activation of the immune system. B cells are a significant contributor to this and other chronic diseases. This project focuses on the role of B cells in perpetuating allergic disease, but will give insights into how B cells contribute to the balance of tolerance versus immune activation in a variety of other diseases, as well.